Dosage forms for the transdermal delivery of narcotic analgesics are well known in the art. For example, U.S. Pat. No. 4,806,341, issued to Chien et al describes transdermal absorption dosage units for narcotic analgesics and antagonist comprising a backing layer, an adjoining layer of a solid polymer matrix containing morphinan narcotic analgesics or antagonist pharmaceuticals and skin permeation enhancers, and an adhesive polymer.
U.S. Pat. No. 4,626,539, issued to Aungst et al describes pharmaceutical compositions containing an opioid, a penetration enhancer such as C.sub.8 -C.sub.18 fatty alcohols or fatty acids, and a pharmaceutical carrier, such as propylene glycol. The compositions may be in gel, lotion or cream form and used in a transdermal patch.
European Patent Publication No. 0368409 describes compositions for the transdermal delivery of buprenorphine salts in a carrier comprising a polar solvent of C.sub.3 -C.sub.4 diols and/or C.sub.3 -C.sub.6 triols and a polar lipid material such fatty alcohols and esters thereof. The compositions may be used in transdermal patches and are described as being useful for analgesic purposes.
U.S. Pat. No. 4,935,428 issued to J. Lewis describes pharmaceutical compositions in sublingual unit dosage for maintenance treatment of opiate addicts comprising from 2-8 milligrams buprenorphine and an amount of naltrexon to attenuate the effect of the buprenorphine when injected. The dosage forms of the '428 patent comprise buprenorphine and naltrexone blended together to form a homogenous mixture or solution.
U.S. Pat. No. 4,464,378 issued to A. Hussain describes dosage forms for nasal administration of narcotic antagonists and analgesics. The dosage forms can be solutions, suspensions, gels or ointments.
U.S. Pat. No. 4,573,995 issued to Chen et al describes transdermal delivery systems for the administration of naloxone, naltrexone and nalbuphine. U.S. Pat. No. 4,588,580 issued to Gale et al describes transdermal delivery systems for delivery of fentanyl and its analgetically effective derivatives.
PCT Patent Publication No. WO 90/04965 describes transdermal dosage forms for delivering narcotic and psychoactive substances which have a reduced potential for abuse. The dosage forms may be in the form of a transdermal patch having a reservoir comprising a homogenous mixture of the narcotic and antagonist, and a releasing means through which the narcotic is released to the body.
The dosage forms of the prior art have deficiencies in that an addict can extract the narcotic from the dosage form for injection or ingestion, or that the narcotic and antagonist are physically combined such that adverse physical and chemical interaction may occur. The present invention overcomes the deficiencies of the prior art dosage forms by providing a transdermal dosage form containing an opioid and an opioid antagonist, wherein the opioid and the antagonist are physically separated by an impermeable barrier. This barrier prevents undesirable ion exchange and other interactions between the opioid and the antagonist. The dosage form of this invention further provides the benefit of being resistive to misuse because the opioid antagonist is released from the dosage form upon being ingested or substantially immersed in water or other solvents. When applied to the skin, the dosage form of this invention delivers only the opioid through the skin and into the systemic circulatory system.
Thus, the dosage form of the present invention provides the following advantages:
1. A therapeutic effect which is constant; PA1 2. Smoothness and consistency in the level of opioid delivered to the bloodstream; PA1 3. Reduced potential for misuse or abuse of the opioid-containing dosage form; PA1 4. Decreased risk of overdosing and resulting toxic reactions; PA1 5. Improvements in the ability of opioid addicts to correctly and safely use opioid maintenance treatment on an outpatient, unsupervised basis; PA1 6. Improved patient compliance with a recommended treatment program; and PA1 7. Elimination of undesirable interactions and reactions between the opioid and the opioid antagonist contained in the dosage form.